tbuckley/cabot-search huggingface dataset:
Tumor necrosis factor alpha delivers exogenous inflammation-related microRNAs to recipient cells with functional targeting capabilities
Authors: Yuechao Zhao, Tan Zhang, Xuelian Shen, Aixue Huang, Hui Li, Lin Wang, Xuemei Liu, Xuejun Wang, Xiang Song, Shengqi Wang, Jie Dong, Ningsheng Shao
Journal: Molecular Therapy (2022)

Tumor necrosis factor alpha (TNF-α) is a critical pro-inflammatory cytokine in a wide range of tumors and infectious diseases. This study showed for the first time that TNF-α could specifically bind to certain intracellular or circulating inflammation-related microRNAs both in vitro and in vivo. The binding sites of TNF-α to microRNAs are located at the N-terminal of TNF-α and the 3'-GGUU motif of microRNAs. TNF-α could deliver exogenous unmodified single-stranded microRNAs into recipient cells through the TNF-α receptors (TNFRs) and stabilize them from being degraded by RNase in cells. Exogenous miR-146a or let-7c delivered into HCT116 cells by TNF-α could escape from lysosomes and specifically downregulate their target genes and then affect cell proliferation and migration in vitro, as well as tumorigenesis in vivo. Based on the above findings, the concept of "non-conjugated ligand-mediated RNA delivery (ncLMRD)" was proposed, which may serve as a promising strategy for therapeutic microRNA delivery in the future.
Active case management to connect hepatitis C notifications to care and treatment in Australia (CONNECT study), a randomised controlled trial
Authors: Tafireyi Marukutira, Karen Moore, Margaret Hellard, Jacqui Richmond, Kate Turner, Alisa Pedrana, Shannon M. Melody, Louise Owen, Wijnand Van Den Boom, Nick Scott, Alexander Thompson, David Iser, Tim Spelman, Mark Veitch, Mark Stoove, Joseph Doyle
Journal: Journal of Hepatology (2022)
The diagnostic accuracy of ElastQ 2-D shear wave elastography for liver fibrosis risk assessment in a mixed etiology, multinational cohort
Authors: David J.M Bauer, Annalisa De Silvestri, Laura Maiocchi, Ruxandra Mare, Ioan Sporea, Theresa Müllner-Bucsics, Giovanna Ferraioli, Thomas Reiberger
Journal: Journal of Hepatology (2022)
Non-invasive prediction of risk of liver-related events in non-alcoholic fatty liver disease patients
Authors: Monica Pons, Jesús Rivera, Grace Lai-Hung Wong, Terry Cheuk-Fung Yip, Adele Delamarre, Tracy Davyduke, M Mang, Salvador Augustin, Juan Manuel Pericàs, Victor de Lédinghen, Vincent Wai-Sun Wong, Juan G Abraldes, Joan Genesca
Journal: Journal of Hepatology (2022)
Presence of HbeAg, HBV DNA in cord blood and down regulation of TLR9 may act as predictive marker for HBV mother to child transmission
Authors: Simanta Kalita, Manash Jyoti Kalita, Gautam Hazarika, Partha Pratim Das, Sangit Dutta, Anjan Jyoti Talukdar, Panchanan Das, Subhash Medhi
Journal: Journal of Hepatology (2022)
Free Light Chains as a potential biomarker of inflammation and fibrosis in non-alcoholic steatohepatitis
Authors: Antonio Liguori, Umberto Basile, Cecilia Napodano, Lidia Tomasello, Fabrizio Mancuso, Luca Di Gialleonardo, Giuseppe Marrone, Marco Biolato, Antonio Gasbarrini, Gian Ludovico Rapaccini, Antonio Grieco, Luca Miele
Journal: Journal of Hepatology (2022)
Driving with Both Feet: Supplementing AKG While Inhibiting BCAT1 Leads to Synthetic Lethality in GBM
Authors: Noah Meurs, Deepak Nagrath
Journal: Cancer Research (2022)

Abstract Understanding how carcinogenesis can expose cancers to synthetically lethal vulnerabilities has been an essential underpinning of development of modern anticancer therapeutics. Isocitrate dehydrogenase wild-type (IDHWT) glioblastoma multiforme (GBM), which is known to have upregulated branched-chain amino acid transaminase 1 (BCAT1) expression, has not had treatments developed to the same extent as the IDH mutant counterpart, despite making up the majority of cases. In this issue, Zhang and colleagues utilize a metabolic screen to identify α-ketoglutarate (AKG) as a synthetically lethal treatment in conjunction with BCAT1 inhibition in IDHWT GBM. These treatments synergize in a multipronged approach that limits substrate catabolism and disrupts mitochondrial homeostasis through perturbing the balance of NAD+/NADH, leading to mTORC1 inhibition and a reduction of nucleotide biosynthesis. Based on these results, the authors propose combination treatment targeting branched chain amino acid catabolism as a potential option for patients with IDHWT GBM. See related article by Zhang et al., p. 2388
Targeting NAE1-mediated protein hyper-NEDDylation halts cholangiocarcinogenesis and impacts on tumour-stroma crosstalk in experimental models
Authors: Paula Olaizola, Pui-Yuen Lee-Law, Maite G. Fernandez-Barrena, Laura Alvarez, Massimiliano Cadamuro, Mikel Azkargorta, Colm O. Rourke, Francisco J. Caballero, Rocio IR Macias, Jose Marin, Marina Serrano-Macia, María Luz Martínez-Chantar, Matías A. Avila, Patricia Aspichueta, Diego Calvisi, Luca Fabris, Felix Elortza, Jesper Andersen, Luis Bujanda, Pedro Miguel Rodrigues, María Jesús Perugorria, Jesus Maria Banales
Journal: Journal of Hepatology (2022)
Hepatitis C elimination in diabetic population from a shared care cascade cohort- under Changhua-Integrated Program to Stop hepatitis C infection (CHIPS-C)
Authors: Tsung-Hui Hu, Yo-Yu Tsao, Wei-Wen Su, Chi-Chao Yang, Chi-Chieh Yang, Sam Li-Sheng Chen, Yen-Po Yeh, Hsiu-Hsi Chen
Journal: Journal of Hepatology (2022)
Distinct hepatocellular carcinoma risks in treated chronic hepatitis C patients with different definitions of advanced chronic liver disease
Authors: Yen-Chun Liu, Cheng Er Hsu, Ya-Ting Cheng, Chung-Wei Su, Chia-Hung Tai, Yi-Cheng Chen, Yi-Chung Hsieh, Wei Teng, Rachel Wen-Juei Jeng, Chun-yen Lin, Rong-Nan Chien, Tai Dar-In, I-Shyan Sheen
Journal: Journal of Hepatology (2022)
National hepatitis elimination profiles: progress towards HBV and HCV elimination in five European countries
Authors: Lindsey Hiebert, Isabelle Nassar, Vanessa Nunez, Loreta Kondili, Sema Mandal, Graham Foster, Francisco Javier Garcia-Samaniego Rey, Philip Bruggmann, Paolo Bonanni, Camila Picchio, Rui Marinho, Jeffrey Lazarus, John Ward
Journal: Journal of Hepatology (2022)
Efficacy and Safety of SH-1028 in Patients With EGFR T790M-Positive NSCLC: A Multicenter, Single-Arm, Open-Label, Phase 2 Trial
Authors: Anwen Xiong, Shengxiang Ren, Huaimin Liu, Liyun Miao, Lei Wang, Jianhua Chen, Wei Li, Runpu Li, Xiang Wang, Zhiwei Lu, Donglin Wang, Xiaohong Wu, Zhihua Liu, Ligang Xing, Yimin Mao, Chunling Liu, Aiping Zeng, Hongrui Niu, Yingying Du, Yuping Sun, Yueyin Pan, Yanping Hu, Xiaodong Zhang, Xueqin Chen, Zhiyong Ma, Na Li, Jianyong Zhang, Min Zhao, Xiaoling Li, Feng Ye, Mingjun Li, Guohua Yu, Xiaomeng Zhang, Jie Min, Dong Han, Jin Li, Caicun Zhou
Journal: Journal of Thoracic Oncology (2022)
Acute severe presentation of autoimmune hepatitis: a 20-year retrospective review of the United States
Authors: Thomas Enke, Daniel Ganger, Jody Rule, Richard Stravitz, Jorge Rakela, Adrian Reuben, Norman Sussman, Anne Larson, Shannan Tujios, Nathan Bass, Sherry Livingston, Valerie Durkalski-Mauldin, William M. Lee
Journal: Journal of Hepatology (2022)
Alcohol-induced changes of inflammatory markers in hepatic and systemic venous blood in early alcohol-related and non-alcoholic fatty liver disease
Authors: Evelina Stankevic, Mads Israelsen, Helene Bæk Juel, Anne Lundager Madsen, Nikolaj Torp, Stine Johansen, Camilla Dalby Hansen, Katrine Prier Lindvig, Bjørn Stæhr Madsen, Maja Thiele, Aleksander Krag, Torben Hansen
Journal: Journal of Hepatology (2022)
Identification of biomarkers of histological response in patients with non-cirrhotic NASH treated with Lanifibranor
Authors: Jerome Boursier, Hugo Herve, Clémence M Canivet, Marine Roux, Pierre Broqua, Michael Cooreman, Jean-Louis Junien, Jean Louis Abitbol, Philippe Huot-Marchand, Lucile Dzen, Sanjaykanumar Patel
Journal: Journal of Hepatology (2022)
A prospective study of global myocardial function in decompensated cirrhosis using advanced echocardiographic techniques and its clinical significance
Authors: Jeyamani Ramachandran, Purendra Kumar Pati, Teresa Hecker, Fadak Mohammadi, Libby John, Vidyaleha Chandran, Matthew Chapman, Yasmina Tashkent, Rosemary McCormick, Kylie Bragg, Majo Joseph, James Gunton, Asif Chinnaratha, Kate Muller, Alan Wigg
Journal: Journal of Hepatology (2022)
Does screening for liver fibrosis change alcohol consumption, diet, and exercise? A prospective cohort study on the consequences of screening in 2, 764 individuals
Authors: Maria Kjærgaard, Katrine Prier Lindvig, Johanne Kragh Hansen, Simon Langkjær Sørensen, Stine Johansen, Katrine Thorhauge, Peter Andersen, Isabel Graupera, Pere Ginès, Aleksander Krag, Maja Thiele
Journal: Journal of Hepatology (2022)
Predictors of HBsAg loss after cessation of nucleo (s)tide analogue therapy in asian patients with low HBsAg levels
Authors: Milan Sonneveld, SM Chiu, Jun Yong Park, Apichat Kaewdech, Wai-Kay Seto, Yasuhito Tanaka, Ivana Carey, Margarita Papatheodoridi, Florian van Bömmel, Sylvia Brakenhoff, Thomas Berg, Fabien Zoulim, Sang Hoon Ahn, George Dalekos, Nicole Erler, Christoph Hoener zu Siederdissen, Heiner Wedemeyer, Markus Cornberg, Man-Fung Yuen, Kosh Agarwal, Andre Boonstra, Maria Buti, T Piratvisuth, George Papatheodoridis, Chien-Hung Chen, Benjamin Maasoumy
Journal: Journal of Hepatology (2022)
Effect of tenofovir disoproxil fumarate treatment on intrahepatic viral burden and liver immune microenvironment in chronic hepatitis B patients with minimally elevated serum alanine aminotransferase
Authors: Abhishek Aggarwal, Ricardo Ramirez, David Pan, Ondrej Podlaha, Jeffrey Wallin, Jaw-Town Lin, Cheng-Hao Tseng, Li Li, Lauri Diehl, Becket Feierbach, Simon Fletcher, Vithika Suri, Yao-Chun Hsu
Journal: Journal of Hepatology (2022)
Performance of the Steatosis-Associated Fibrosis Estimator (SAFE) to predict F2 fibrosis and higher in a cohort of South Korean patients with non-alcoholic fatty liver disease (NAFLD)
Authors: Vivek Charu, Allison Kwong, Ajitha Mannalithara, Eileen Yoon, Dae Won Jun, W.Ra Kim
Journal: Journal of Hepatology (2022)
PRIME-HCC: phase Ib study of neoadjuvant ipilimumab and nivolumab prior to liver resection for hepatocellular carcinoma
Authors: Antonio D’Alessio, Madhava Pai, Duncan Spalding, Poyyamozhi Rajagopal, Thomas Talbot, Robert Goldin, Claudia Angela Maria Fulgenzi, Caroline Ward, Vincent Yip, Tony Dhillon, Sarah Slater, Mikael Sodergren, Paul Tait, Nagy Habib, Robert Thomas, Alessio Cortellini, Rohini Sharma, David J. Pinato
Journal: Journal of Hepatology (2022)
Characterising the early inflammatory landscape of primary sclerosing cholangitis
Authors: Calli Dendrou, Kate Lynch, Fabiola Curion, Charlotte Rich-Griffin, Hing-Yuen Yeung, Nicholas Provine, Nicholas Ilott, Helen Ferry, Eve Fryer, Holm Uhlig, Roger W.G. Chapman, Satish Keshav, Paul Klenerman
Journal: Journal of Hepatology (2022)
Acute hepatitis after COVID-19 vaccine: case series by the International autoimmune hepatitis group (IAIHG) and the european reference network on hepatological diseases (ERN RARE-LIVER)
Authors: Greta Codoni, Maria Alejandra Gracia Villamil, Albert Stättermayer, Agustin Castiella, Christoph Schramm, Jan-Philipp Weltzsch, Marcial Sebode, Christine Bernsmeier, Wikrom Karnsakul, Ana Lleo, Tom Gevers, Limas Kupcinskas, Nélia Hernandez, Andreas Cerny, Michele Ghielmetti, Diego Vergani, Giorgina Mieli-Vergani, Jose Pinazo Bandera, Maria Isabel Lucena, Raul J. Andrade, Yoh Zen, Richard Taubert
Journal: Journal of Hepatology (2022)
Post-operative complications and short-term survival in obese cirrhotic patients undergoing liver transplantation
Authors: Javier Tejedor-Tejada, Carmen Alonso Martin, Samuel Juan Fernández Prada, Laura Juan, Violeta Mauriz, Abdelaleem Helal, Rifaat Safadi, Esteban Fuentes Valenzuela, Carolina Almohalla, Félix García Pajares
Journal: Journal of Hepatology (2022)
Progression of liver disease among patients with a new diagnosis of protease inhibitor ZZ alpha-1 antitrypsin deficiency
Authors: Harmeet Malhi, Tiffany Wu, May Hagiwara, Gregory Donadio, Esteban Gnass, Will Treem, Kaili Ren, Ed G. Marins, Chitra Karki
Journal: Journal of Hepatology (2022)
Antibody and cellular immune responses following dual COVID-19 vaccination within infection-naive residents of long-term care facilities: an observational cohort study
Authors: Gokhan Tut, Tara Lancaster, Panagiota Sylla, Megan S Butler, Nayandeep Kaur, Eliska Spalkova, Christopher Bentley, Umayr Amin, Azar Jadir, Samuel Hulme, Morenike Ayodele, David Bone, Elif Tut, Rachel Bruton, Maria Krutikov, Rebecca Giddings, Madhumita Shrotri, Borscha Azmi, Christopher Fuller, Verity Baynton, Aidan Irwin-Singer, Andrew Hayward, Andrew Copas, Laura Shallcross, Paul Moss
Journal: The Lancet Healthy Longevity (2022)
Sarcopenia increases the risk of cirrhosis disease progression and death in patients with cirrhosis
Authors: Puneeta Tandon, Sarah Wang, Moon Young Kim, Bart Van Hoek, Daphne Bot, Jeroen van Vugt, Berend Beumer, Jan Ijzermans, Sunil Taneja, Surender Singh, Maryam Ebadi, Aldo J Montano-Loza
Journal: Journal of Hepatology (2022)
CRIVALVIR-FOCUS: low HIV and chronic Hepatitis B and C infection prevalence among women in reproductive and sexual health services in Valencia, Spain
Authors: Miguel Garcia-Deltoro, Pilar Obon, Caterina Canapele, Jose Maria Mari, Adela Vidal, Maria Martinez-Roma, Maria Dolores Ocete, Concepción Gimeno Cardona, Moisés Diago, Neus Gomez-Muñoz, Alba Carrodeguas, Diogo Medina, Enrique Ortega González
Journal: Journal of Hepatology (2022)
Long-term follow-up of HCV resistance-associated substitutions after DAA treatment failure
Authors: Julia Dietz, Beat Müllhaupt, Peter Buggisch, Christiana Graf, Kai-Henrik Peiffer, Katrin Matschenz, Jörn Schattenberg, Stefan Mauss, Christoph Antoni, Elena Durmashkina, Claus Niederau, Thomas Discher, Janina Trauth, Georg Dultz, Julian Schulze zur Wiesch, Felix Piecha, Hartwig Klinker, Tobias Müller, Christoph Neumann-Haefelin, Thomas Berg, Christoph Berg, Stefan Zeuzem, Christoph Sarrazin
Journal: Journal of Hepatology (2022)
The long-term effect of Hepatitis C eradication by direct-acting antivirals on patient’s mood and quality of life as determined by the Beck’s Depression Inventory and EQ5D Quality of Life questionnaires-a single unit study
Authors: Aoife Alvain, Sarah Lanigan, Mary Bohan-Keane, Margaret Scarry, Lynda Jordan, Cynthia Garvey, Priyanka Jose, John Lee
Journal: Journal of Hepatology (2022)
Incidence and risk factors of hepatitis C liver morbidity and mortality in the era of direct-acting antiviral therapies: a population-based linkage study
Authors: Maryam Alavi, Heather Valerio, Matthew Law, Ian Lockart, Mark Danta, Jason Grebely, Janaki Amin, Behzad Hajarizadeh, Jacob George, Gregory Dore
Journal: Journal of Hepatology (2022)
Non-alcoholic fatty liver disease features a reduced reverse polyunsaturated fatty acid transport (free fatty acids/high-density lipoprotein) from the periphery to the liver
Authors: Gabriele Mocciaro, Michael Allison, Benjamin Jenkins, Vian Azzu, Isabel Huang-Doran, Richard Kay, Antonio Murgia, Davies Susan, Mattia Frontini, Antonio Vidal-Puig, Albert Koulman, Julian L. Griffin, Michele Vacca
Journal: Journal of Hepatology (2022)
Liver transplant patients infection rate with SARS-CoV-2 is lower but depend upon the infection rate in the general population and have a better outcome
Authors: Michal Cohen-Naftaly, Evelin Oxtrud, Orly Sneh Arbib, Assaf Issachar, Yael Harif, Amir Shlomai, Marius Braun
Journal: Journal of Hepatology (2022)
Real world validation of BAVENO-7 non-invasive diagnosis for clinically significant portal hypertension in compensated advanced chronic liver disease: international cohort study
Authors: Yu Jun Wong, Junhui, Garrett Kang, Elisabetta Degasperi, Giulia Tosetti, Sanchit Sharma, Chuan Liu, Jia Li, Xiaolong Qi, Anoop Saraya, Massimo Primignani
Journal: Journal of Hepatology (2022)
Cold shock protein YB-1 upregulates MDR1 transcription and thus contributes to chemoresistance against cisplatin treatment in cholangiocarcinoma
Authors: Tao Lin, Jonathan A. Lindquist, Peter Rene Mertens, Matthias Ebert, Steven Dooley, Jun Li, Stefan Munker, Honglei Weng
Journal: Journal of Hepatology (2022)
Development of a novel MRCP-score for patients with primary sclerosing cholangitis, and assessment of agreement and prognostic value
Authors: Aristeidis Grigoriadis, Kristina Ringe, Johan Bengtsson, Erik Fridh Baubeta, Cecilia Forsman, Nafsika Korsavidou-Hult, Fredrik Rorsman, Emma Nilsson, Nikolaos Kartalis, Annika Bergquist
Journal: Journal of Hepatology (2022)
Peripheral blood mononuclear cells mitochondrial copy number and adenosine triphosphate inhibition test in non-alcoholic fatty liver disease
Authors: Eileen Yoon, Dae Won Jun, Sang Bong Ahn, Huiyul Park, Hyo Young Lee, Hyunwoo Oh, Chul-min Lee, Mi Mi Kim, Bo-Kyeong Kang, Joo Hyun Sohn
Journal: Journal of Hepatology (2022)
Lonafarnib combination with peginterferon Lambda diminished triphasic HDV kinetic pattrn seen under Lambda monotherapy: the LIFT HDV study
Authors: Sarah Duehren, Christopher Koh, Julian Hercun, Farial Rahman, Pallavi Surana, Anusha Vittal, Walter Lai, Ohad Etzion, Scott Cotler, Jeffrey Glenn, Harel Dahari, Theo Heller
Journal: Journal of Hepatology (2022)
Different immunological microenvironment in patients with different cirrhosis etiology and hepatocellular carcinoma
Authors: Andrea Dalbeni, Leonardo Natola, Filippo Cattazzo, Antonio Vella, Marta Garbin, Michele Bevilacqua, Anna Mantovani, Giovanna Zanoni, Alfredo Guglielmi, Michele Milella, David Sacerdoti
Journal: Journal of Hepatology (2022)
Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312): a multicentre, open-label, randomised, phase 3 trial
Authors: Robin Kate Kelley, Lorenza Rimassa, Ann-Lii Cheng, Ahmed Kaseb, Shukui Qin, Andrew X Zhu, Stephen L Chan, Tamar Melkadze, Wattana Sukeepaisarnjaroen, Valery Breder, Gontran Verset, Edward Gane, Ivan Borbath, Jose David Gomez Rangel, Baek-Yeol Ryoo, Tamta Makharadze, Philippe Merle, Fawzi Benzaghou, Kamalika Banerjee, Saswati Hazra, Jonathan Fawcett, Thomas Yau
Journal: The Lancet Oncology (2022)

Cabozantinib has shown clinical activity in combination with checkpoint inhibitors in solid tumours. The COSMIC-312 trial assessed cabozantinib plus atezolizumab versus sorafenib as first-line systemic treatment for advanced hepatocellular carcinoma.
Model to predict on-treatment restoration of functional HBV-specific CD8+ cell response foresees off-treatment HBV control in eAg-negative chronic hepatitis B
Authors: Julia Peña Asensio, Henar Calvo, Joaquin Miquel, Eduardo Sanz de Villalobos, Alejandro González Praetorius, Miguel Torralba, Juan Ramón Larrubia
Journal: Journal of Hepatology (2022)
Five years of progress towards achieving hepatitis C elimination in the country of Georgia, April 2015-October 2021
Authors: Tengiz Tsertsvadze, Amiran Gamkrelidze, Nikoloz Chkhartishvili, Akaki Abutidze, Lali Sharvadze, Vakhtang Kerashvili, Maia Butsashvili, David Metreveli, Lia Gvinjilia, Tinatin Kuchuloria, Shaun Shadaker, Tamar Gabunia, Ekaterine Adamia, Stefan Zeuzem, Nezam Afdhal, Sanjeev Arora, Karla Thornton, Paige A Armstrong
Journal: Journal of Hepatology (2022)
Overall mortality in patients with chronic hepatitis C: major effects of social vulnerability, tobacco smoking, and history of unhealthy alcohol use (ANRS CO22 HEPATHER cohort)
Authors: Lauren Perieres, Fabrice Carrat, Marta Lotto, Celine Dorival, Clémence Ramier, Fabienne Marcellin, Carole Cagnot, Elizabeth Delarocque-Astagneau, Patrizia Carrieri, Stanislas Pol, Helene Fontaine, Camelia Protopopescu
Journal: Journal of Hepatology (2022)
Identification of new potential biomarkers to follow steatohepatitis in patients with non-alcoholic/metabolic-associated fatty liver disease
Authors: Douglas Maya, Rocío Gallego-Durán, María del Rosario García-Lozano, Rocio Munoz Hernandez, Angela Rojas Alvarez-Ossorio, Antonio Gil-Gomez, Javier Ampuero, Manuel Romero Gomez
Journal: Journal of Hepatology (2022)
In severe alcohol-related hepatitis, hepatocyte ballooning correlates with expression of p16 and components of a secretory phenotype that has been associated with cellular senescence
Authors: Nikhil Vergis, Isabelle Hall, Callum Arthurs, Hiromi Kudo, Stephen Atkinson, David Shapiro, Michael Lutz, Birgit Jung, Markus Weissbach, Wolfgang Albrecht, Luke D. Tyson, Tong Liu, Emma Lord, Lars Zender, Mark Thursz, Robert D. Goldin
Journal: Journal of Hepatology (2022)
The MRI and AST (MAST) score is correlated with noninvasive and histologic markers of fibrosis in patients with advanced fibrosis due to NASH
Authors: Mazen Noureddin, Kris V. Kowdley, Anita Kohli, Aasim Sheikh, Guy Neff, Bal Raj Bhandari, Nadege Gunn, Stephen Caldwell, Zachary Goodman, Dora Ding, Lily Ma, Jay Chuang, Ryan Huss, Chuhan Chung, Robert Myers, Keyur Patel, Brian Borg, Reem Ghalib, John Poulos, Ziad H. Younes, Magdy Elkhashab, Tarek Hassanein, Rajalakshmi Iyer, Peter Ruane, Mitchell Shiffman, Simone Strasser, Vincent Wai-Sun Wong, Rohit Loomba, Naim Alkhouri
Journal: Journal of Hepatology (2022)
Treating children with HCV close to home through a virtual national multidisciplinary network
Authors: Deirdre Kelly, Carla Lloyd, Maxine Brown, Kinza Ahmed, Ivana Carey, Sarah Tizzard, Joanne Crook, Penny North-Lewis, Palaniswamy Karthikeyan, Sanjay Bansal, Graham Foster
Journal: Journal of Hepatology (2022)
PRC2-Inactivating Mutations in Cancer Enhance Cytotoxic Response to DNMT1-Targeted Therapy via Enhanced Viral Mimicry
Authors: Amish J. Patel, Sarah Warda, Jesper L.V. Maag, Rohan Misra, Miguel A. Miranda-Román, Mohini R. Pachai, Cindy J. Lee, Dan Li, Naitao Wang, Gabriella Bayshtok, Eve Fishinevich, Yinuo Meng, Elissa W.P. Wong, Juan Yan, Emily Giff, Melissa B. Pappalardi, Michael T. McCabe, Jonathan A. Fletcher, Charles M. Rudin, Sarat Chandarlapaty, Joseph M. Scandura, Richard P. Koche, Jacob L. Glass, Cristina R. Antonescu, Deyou Zheng, Yu Chen, Ping Chi
Journal: Cancer Discovery (2022)

Abstract Polycomb repressive complex 2 (PRC2) has oncogenic and tumor-suppressive roles in cancer. There is clinical success of targeting this complex in PRC2-dependent cancers, but an unmet therapeutic need exists in PRC2-loss cancer. PRC2-inactivating mutations are a hallmark feature of high-grade malignant peripheral nerve sheath tumor (MPNST), an aggressive sarcoma with poor prognosis and no effective targeted therapy. Through RNAi screening in MPNST, we found that PRC2 inactivation increases sensitivity to genetic or small-molecule inhibition of DNA methyltransferase 1 (DNMT1), which results in enhanced cytotoxicity and antitumor response. Mechanistically, PRC2 inactivation amplifies DNMT inhibitor–mediated expression of retrotransposons, subsequent viral mimicry response, and robust cell death in part through a protein kinase R (PKR)–dependent double-stranded RNA sensor. Collectively, our observations posit DNA methylation as a safeguard against antitumorigenic cell-fate decisions in PRC2-loss cancer to promote cancer pathogenesis, which can be therapeutically exploited by DNMT1-targeted therapy. Significance: PRC2 inactivation drives oncogenesis in various cancers, but therapeutically targeting PRC2 loss has remained challenging. Here we show that PRC2-inactivating mutations set up a tumor context–specific liability for therapeutic intervention via DNMT1 inhibitors, which leads to innate immune signaling mediated by sensing of derepressed retrotransposons and accompanied by enhanced cytotoxicity. See related commentary by Guil and Esteller, p. 2020. This article is highlighted in the In This Issue feature, p. 2007
Systemic treatments with tyrosine kinase inhibitors and platinum-based chemotherapy in patients with unresectable or metastatic hepato-cholangiocarcinoma
Authors: Elia Gigante, Christian Hobeika, Brigitte Le Bail, Valérie Paradis, David Tougeron, Marie Lequoy, Mohamed Bouattour, Jean-Frédéric Blanc, Nathalie Ganne-Carrié, Henri Tran, Clemence Hollande, Manon Allaire, Giuliana Amaddeo, Helene Regnault, Paul Vigneron, Maxime Ronot, Laure Elkrief, Gontran Verset, Eric Trepo, Aziz Zaanan, Marianne Ziol, Massih Ningarhari, Julien Calderaro, Julien Edeline, Jean Charles Nault
Journal: Journal of Hepatology (2022)